This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The basidiomycete Cryptococcus neoformans is responsible for the most common systemic fungal infection in HIV patients. This infection depends upon several properties of the fungus, including its ability to grow at human body temperature, its polysaccharide capsule, and its production of cell wall-associated melanin, each of which is controlled by complex gene expression programs. We seek to explore the role of RNA interference in Cryptococcus gene expression regulation. Interestingly, although RNAi is known to be active in Cryptococcus, its complement of RNAi proteins appears to be distinctively diversified as compared to other basidiomycetes. Thus, characterization of the mechanism of RNAi and its genetic targets in this organism could both further our understanding of Cryptococcus pathogenesis and also provide a unique new model system for the study of RNA interference and noncoding RNA.